AstraZeneca UK Limited

Section 4.3

Replacement of paragraph 1:

‘Bricanyl solution for injection should not be used as a tocolytic agent in patients with pre-existing ischaemic heart disease or those patients with significant risk factors for ischaemic heart disease.’

Replacement of bullet point:

·         ‘any condition of the mother or foetus in which prolongation of the pregnancy is hazardous, e.g. severe toxaemia, anti-partum haemorrhage, intra-uterine infection, intrauterine infection, severe preeclampsia, abruptio placentae, threatened abortion during the 1^st and 2^nd trimester, or cord compression.’

Addition of last paragraph:

‘Bricanyl solution for injection should not be used in patients with a history of hypersensitivity to any of the ingredients.’

Section 4.4

Replacement of text with:

‘As for all beta₂-agonists caution should be observed in patients with thyrotoxicosis.

Cardiovascular effects may be seen with sympathomimetic drugs, including Bricanyl. There is some evidence from post-marketing data and published literature of myocardial ischaemia associated with beta agonists.

Due to the positive inotropic effect of the beta₂-agonists, these drugs should not be used in patients with hypertrophic cardiomyopathy.

Tocolysis
Bricanyl should be used with caution in tocolysis and supervision of cardiorespiratory function, including ECG monitoring, should be considered. Treatment should be discontinued if signs of myocardial ischaemia (such as chest pain or ECG changes) develop. Bricanyl should not be used as a tocolytic agent in patients with significant risk factors for or pre-existing heart disease (see section 4.3, Contraindications).

In premature labour in a patient with known or suspected cardiac disease, a physician experienced in cardiology should assess the suitability of treatment before intravenous infusion with Bricanyl.

In order to minimise the risk of hypotension associated with tocolytic therapy, special care should be taken to avoid caval compression by keeping the patient in the left or right lateral positions throughout the infusion.

In treatment of premature labour, hyperglycaemia and ketoacidosis have been found in pregnant women with diabetes after treatment with beta₂-agonists. It may therefore be necessary to adjust the insulin dose when beta₂-agonists are used in the treatment.

Increased tendency to uterine bleeding has been reported in connection with Caesarian section. However, this can be effectively stopped by propranolol 1-2 mg injected intravenously.

Respiratory indications
Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving Bricanyl should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease.

Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.

Due to the hyperglycaemic effects of beta₂-agonists, additional blood glucose controls are recommended initially in diabetic patients.

Potentially serious hypokalaemia may result from beta₂-agonist therapy. Particular caution is recommended in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalaemic effect may be potentiated by concomitant treatments (see section 4.5, Interactions). It is recommended that serum potassium levels are monitored in such situations.

If a previously effective dosage regimen no longer gives the same symptomatic relief, the patient should urgently seek further medical advice. Consideration should be given to the requirements for additional therapy (including increased dosages of anti-inflammatory medication). Severe exacerbations of asthma should be treated as an emergency in the usual manner.’

Section 4.8

Replacement of text with:

‘The intensity of the adverse reactions depends on dosage and route of administration. An initial dose titration will often reduce the adverse reactions. Most of the adverse reactions  are characteristic of sympathomimetic amines. The majority of these effects have reversed spontaneously within the first 1-2 weeks of treatment.

The frequency of side effects is low at the recommended doses.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100 and <1/10), uncommon (>1/1,000 and <1/100), rare (>1/10,000 and <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Bronchial asthma. Chronic bronchitis, emphysema and other lung diseases where bronchospasm is a complicating factor.

^# A few patients feel tense; this is also due to the effects on skeletal muscle and not to direct CNS stimulation.

^ Reported spontaneously in post-marketing data and therefore frequency regarded as unknown

* In rare cases, through unspecified mechanisms, paradoxical bronchospasm may occur, with wheezing immediately after inhalation. This should be immediately treated with a rapid-onset bronchodilator. Bricanyl therapy should be discontinued and after assessment, an alternative therapy initiated.

Preterm labour

# A few patients feel tense; this is also due to the effects on skeletal muscle and not to direct CNS stimulation.

^ Reported spontaneously in post-marketing data and therefore frequency regarded as unknown

* In rare cases, through unspecified mechanisms, paradoxical bronchospasm may occur, with wheezing immediately after inhalation. This should be immediately treated with a rapid-onset bronchodilator. Bricanyl therapy should be discontinued and after assessment, an alternative therapy initiated.

During treatment of preterm labour, when high doses of Bricanyl are used, diabetic mothers may develop hyperglycaemia and lactacidosis. In these patients glucose and acid-base balance should be carefully monitored. High doses of beta₂-stimulants may cause hypokalaemia as a result of redistribution of potassium. Symptoms of pulmonary oedema have also been reported following treatment of preterm labour, in some cases this has proved fatal. Predisposing factors include fluid overload, multiple pregnancy, pre-existing cardiac disease and maternal infection. Close monitoring of the patient’s state of hydration is essential. If signs of pulmonary oedema develop (e.g. cough, shortness of breath), treatment should be discontinued immediately and diuretic therapy instituted.

An increased tendency to bleeding has been described in connection with caesarean section (give propranolol, 1-2 mg i.v.) in patients treated with Bricanyl for preterm labour.’

Section 9

Change of date:

4^th June 2002 / 12^th May 2007

Section 10

Change of date:

30^th March 2009